DESCRIPTION: The goals of this research program are to identify the genetic lesions responsible for T-ALL and to determine how these defects promote leukemogenesis. Tumor-specific activation of the TAL1 gene is the most common genetic lesion associated with T-ALL. Therefore, to understand the role of TAL1 in the pathogenesis of T-ALL, the following specific aims will be pursued. First, the functional properties of TAL1 polypeptides will be examined by characterizing the cellular proteins that associate with them during normal (i.e., erythroid) and neoplastic (T-ALL) development. Second, the malignant potential of TAL1 will be explored by targeted expression of TAL1 transgenes in the T cell compartment of mice. Finally, an attempt will be made to identify novel TAL1-related genes that may also play a role in the formation of T-ALL.